Monitoring of SARS-CoV-2 seroprevalence among primary healthcare patients in the Barcelona Metropolitan Area: the SeroCAP sentinel network protocol

COVID-19; Epidemiology; Primary careCOVID-19; Epidemiología; Atención primariaCOVID-19; Epidemiologia; Atenció primàriaIntroduction SARS-CoV-2 seroprevalence studies are currently being recommended and implemented in many countries. Forming part of the COVID-19 monitoring and evaluation plan of the Catalan Government Health Department, our network aims to initiate a primary healthcare sentinel monitoring system as a surrogate of SARS-CoV-2 exposure in the Barcelona Metropolitan Area. Methods and analysis The seroCAP is a serial cross-sectional study, which will be performed in the Barcelona Metropolitan Area to estimate antibodies against SARS-CoV-2. From February 2021 to March 2022, the detection of serum IgG antibodies against SARS-CoV-2 trimeric spike protein will be performed on a monthly basis in blood samples collected for diverse clinical purposes in three reference hospitals from the three Barcelona healthcare areas (BCN areas). The samples (n=2588/month) will be from patients attended by 30 primary healthcare teams at 30 basic healthcare areas (BHA). A lab software algorithm will systematically select the samples by age and sex. Seroprevalence will be estimated and monitored by age, sex, BCN area and BHA. Descriptive and cluster analysis of the characteristics and distribution of SARS-CoV-2 infections will be performed. Sociodemographic, socioeconomic and morbidity-associated factors will be determined using logistic regression. We will explore the association between seroprevalence, SARS-CoV-2 confirmed cases and the implemented measures using interrupted time series analysis. Ethics and dissemination Ethical approval was obtained from the University Institute Foundation for Primary Health Care Research Jordi Gol i Gurina ethics committee. An informed consent is not required regarding the approval of the secondary use of biological samples within the framework of the COVID-19 pandemic. A report will be generated quarterly. The final analysis, conclusions and recommendations will be shared with the stakeholders and communicated to the general public. Manuscripts resulting from the network will be submitted for publication in peer-reviewed journals.This work will be supported by the Health Department of the Government of Catalunya (No grant number)

Monitoring COVID‐19 vaccine effectiveness against COVID‐19 hospitalisation and death using electronic health registries in ≥65 years old population in six European countries, October 2021 to November 2022

Background: Within the ECDC-VEBIS project, we prospectively monitored vaccine effectiveness (VE) against COVID-19 hospitalisation and COVID-19-related death using electronic health registries (EHR), between October 2021 and November 2022, in community-dwelling residents aged 65-79 and ≥80 years in six European countries. Methods: EHR linkage was used to construct population cohorts in Belgium, Denmark, Luxembourg, Navarre (Spain), Norway and Portugal. Using a common protocol, for each outcome, VE was estimated monthly over 8-week follow-up periods, allowing 1 month-lag for data consolidation. Cox proportional-hazards models were used to estimate adjusted hazard ratios (aHR) and VE = (1 - aHR) × 100%. Site-specific estimates were pooled using random-effects meta-analysis. Results: For ≥80 years, considering unvaccinated as the reference, VE against COVID-19 hospitalisation decreased from 66.9% (95% CI: 60.1; 72.6) to 36.1% (95% CI: -27.3; 67.9) for the primary vaccination and from 95.6% (95% CI: 88.0; 98.4) to 67.7% (95% CI: 45.9; 80.8) for the first booster. Similar trends were observed for 65-79 years. The second booster VE against hospitalisation ranged between 82.0% (95% CI: 75.9; 87.0) and 83.9% (95% CI: 77.7; 88.4) for the ≥80 years and between 39.3% (95% CI: -3.9; 64.5) and 80.6% (95% CI: 67.2; 88.5) for 65-79 years. The first booster VE against COVID-19-related death declined over time for both age groups, while the second booster VE against death remained above 80% for the ≥80 years. Conclusions: Successive vaccine boosters played a relevant role in maintaining protection against COVID-19 hospitalisation and death, in the context of decreasing VE over time. Multicountry data from EHR facilitate robust near-real-time VE monitoring in the EU/EEA and support public health decision-making.European Centre for Disease Prevention and Control, Grant/Award Numbers ECDC/2021/018, RS/2022/DTS/24104.info:eu-repo/semantics/publishedVersio

Monitoring of SARS-CoV-2 seroprevalence among primary healthcare patients in the Barcelona Metropolitan Area: the SeroCAP sentinel network protocol

Introduction SARS-CoV-2 seroprevalence studies are currently being recommended and implemented in many countries. Forming part of the COVID-19 monitoring and evaluation plan of the Catalan Government Health Department, our network aims to initiate a primary healthcare sentinel monitoring system as a surrogate of SARS-CoV-2 exposure in the Barcelona Metropolitan Area. Methods and analysis The seroCAP is a serial cross-sectional study, which will be performed in the Barcelona Metropolitan Area to estimate antibodies against SARS-CoV-2. From February 2021 to March 2022, the detection of serum IgG antibodies against SARS-CoV-2 trimeric spike protein will be performed on a monthly basis in blood samples collected for diverse clinical purposes in three reference hospitals from the three Barcelona healthcare areas (BCN areas). The samples (n=2588/month) will be from patients attended by 30 primary healthcare teams at 30 basic healthcare areas (BHA). A lab software algorithm will systematically select the samples by age and sex. Seroprevalence will be estimated and monitored by age, sex, BCN area and BHA. Descriptive and cluster analysis of the characteristics and distribution of SARS-CoV-2 infections will be performed. Sociodemographic, socioeconomic and morbidity-associated factors will be determined using logistic regression. We will explore the association between seroprevalence, SARS-CoV-2 confirmed cases and the implemented measures using interrupted time series analysis. Ethics and dissemination Ethical approval was obtained from the University Institute Foundation for Primary Health Care Research Jordi Gol i Gurina ethics committee. An informed consent is not required regarding the approval of the secondary use of biological samples within the framework of the COVID-19 pandemic. A report will be generated quarterly. The final analysis, conclusions and recommendations will be shared with the stakeholders and communicated to the general public. Manuscripts resulting from the network will be submitted for publication in peer-reviewed journals

Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial

No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19.The authors thank Gerard Carot-Sans, PhD, for providing medical writing support during the revisions of the subsequent drafts of the manuscript; the personnel from the Fights Aids and Infectious Diseases Foundation for their support in administration, human resources and supply chain management; Eric Ubals (Pierce AB) and Òscar Palao (Opentic) for website and database management; Óscar Camps and OpenArms nongovernmental organization for nursing home operations; and Anna Valentí and the Hospital Germans Trias i Pujol Human Resources Department for telephone monitoring. We thank Consorci Sanitari del Maresme, Centre Sociosanitari El Carme, l'Hospital General de Granollers and occupational hazards department of Hospital Germans Trias i Pujol for their contribution with patient enrollment. We are very grateful to Marc Clotet and Natalia Sánchez who coordinated the JoEmCorono crowd-funding campaign. We thank the Hospital Germans Trias Pujol Institutional Review Board and the Spanish Agency of Medicines and Medical Devices for their prompt action for consideration and approvals to the protocol. Financial support. This work was mainly supported by the crowd-funding campaign JoEmCorono (https://www.yomecorono.com/) with contributions from more than 72 000 citizens and corporations. The study also received financial support from Laboratorios Rubió, Laboratorios Gebro Pharma, Zurich Seguros, SYNLAB Barcelona, and Generalitat de Catalunya. Laboratorios Rubió also contributed to the study with the required doses of hydroxychloroquine (Dolquine®). Foundation Dorneur partly funded lab equipment at Irsi-Caixa.Peer reviewe

La vigilancia epidemiológica desde una aproximación sindémica: la vigilancia de las infecciones de transmisión sexual y de la tuberculosis centrada en poblaciones a riesgo de infección

El propósito principal de la tesis es contribuir en lo posible a potenciar la vigilancia de las pandemias de las infecciones de transmisión sexual (ITS) y la tuberculosis (TB) en las poblaciones a riesgo de infección a través de una aproximación y un análisis sindémico para facilitar el diseño de intervenciones eficaces de prevención y control. Se llevaron a cabo cinco estudios en Cataluña y Portugal incluyendo distintos diseños epidemiológicos: incidencia poblacional, cohortes retrospectivas, y series temporales, y realizándose análisis descriptivos, modelos de regresión, análisis de series temporales y de clústeres. Los resultados mostraron como durante los últimos años, en Barcelona y Cataluña, hubo un aumento drástico de los casos notificados de ITS sobre todo en jóvenes, especialmente en mujeres jóvenes. Factores como ser hombre, el número de parejas o episodios previos de ITS o vivir en zonas urbanas se asociaron con el riesgo de presentar coinfección por el VIH. Se identificaron y caracterizaron tres clústeres diferenciados de casos de ITS en Cataluña. Durante la pandemia por COVID-19 hubo una reducción marcada en los casos diagnosticados y notificados de ITS, siendo esta disminución más pronunciada en mujeres y personas jóvenes. En los estudios relacionados con la TB, los resultados muestran cómo durante los últimos años la magnitud de la tendencia descendente en el número de casos notificados en Portugal fue desigual en las distintas poblaciones analizadas (menor en personas de nacionalidad no portuguesa, niños menores de 5 años y en personas VIH negativas). La falta de adherencia al tratamiento de la infección tuberculosa latente estuvo asociada a pautas largas del tratamiento y con determinados factores socio- epidemiológicos, clínicos y de comportamiento, que variaban en las dos áreas metropolitanas analizadas y que incluían factores como tener más de 15 años, haber nacido en el extranjero, tener una enfermedad crónica, el abuso de alcohol y el ser una persona que se inyecta drogas.El propòsit principal de la tesi és contribuir en la mesura del possible a potenciar la vigilància de les pandèmies de les infeccions de transmissió sexual (ITS) i la tuberculosi (TB) en les poblacions a risc d’infecció a través d'una aproximació i una anàlisi sindèmica per a facilitar el disseny d'intervencions eficaces de revenció i control. Es van dur a terme cinc estudis a Catalunya i Portugal incloent diferents dissenys epidemiològics (incidència poblacional, cohorts retrospectives, i sèries temporals), i fent anàlisis descriptives, models de regressió, anàlisis de sèries temporals i de clústers. Els resultats van mostrar com durant els darrers anys, a Barcelona i Catalunya, va haver-hi un augment dràstic dels casos notificats d'ITS sobretot en joves, especialment en dones joves. Factors com ara ser home, el nombre de parelles o episodis previs d’ITS, o viure en zones urbanes, es van associar amb un major risc de presentar coinfecció pel VIH. Es van identificar i caracteritzar tres clústers diferenciats de casos d'ITS a Catalunya. Durant la pandèmia de la COVID-19 va haver-hi una reducció marcada en el diagnòstic i notificació de casos d’ITS, aquesta disminució va ser més pronunciada en dones i persones joves. En els estudis relacionats amb la TB, els resultats mostren com la magnitud de la tendència descendent en el nombre de casos notificats a Portugal els darrers anys va ser desigual en les diferents poblacions analitzades (menor en persones de nacionalitat no portuguesa, nens menors de 5 anys i en persones VIH negatives). La manca d’adherència al tractament de la infecció tuberculosa latent va estar associada amb pautes llargues del tractament i amb determinats factors socioepidemiològics, clínics i de comportament, que variaven en les dues àrees metropolitanes analitzades i que incloïen factors com ara tenir més de 15 anys, haver nascut a l'estranger, tenir una malaltia crònica, l’abús d'alcohol i ser una persona que s’injecta drogues.The main purpose of this thesis is to contribute as much as possible to enhance the surveillance of sexually transmitted infections (STIs) and tuberculosis (TB) pandemics in at-risk populations through a syndemic approach, and to facilitate the design of effective prevention and control interventions. Five studies with different epidemiological designs (population-based incidence, retrospective cohorts, and time series) were carried out in Catalonia and Portugal. Descriptive analysis, regression models, and time series and clustering analysis were performed. Findings from the STI analysis showed that in recent years, there has been a sharp increase in reported cases of STIs in Barcelona and Catalonia, especially in young people, particularly young women. Factors such as male sex, number of partners, number of previous STI episodes, and living in urban areas were associated with higher risk of HIV coinfection. Three differentiated clusters of STI cases in Catalonia were identified and characterised. During the COVID-19 pandemic there was a drastic reduction in diagnosed and reported cases of STIs; this decrease was more pronounced in women and young people. Findings from the TB analysis showed that in recent years the magnitude of the decrease in cases reported in Portugal differed across different populations (smaller decreases in people of nonPortuguese nationality, children under five years of age, and in HIV-negative people). Poor adherence to medications for latent TB infection was associated with long courses of treatment and with certain socioepidemiological, clinical, and behavioural factors such as age above 15 years, being born abroad, concomitant chronic disease, alcohol abuse, and injection drug use. The main associating factors differed between the two metropolitan areas analysed

Portugal Plano Nacional de Saúde em Números, 2015: Revisão e Extensão a 2020

O documento Plano Nacional de Saúde: Revisão e Extensão a 2020 constituiu-se como agregador e orientador das medidas consideradas mais relevantes para a obtenção de mais ganhos em saúde por parte da população residente em Portugal; mantendo assim o foco que o Plano já tinha anteriormente de, com esses ganhos, reduzir e minimizar desigualdades existentes

The prognostic significance of glomerular infiltrating leukocytes during acute renal allograft rejection

Transplant glomerulitis, observed in T cell-mediated and antibody-mediated rejection, is histologically characterized by intracapillary mononuclear cell infiltration. However, the prognostic value of counting various glomerular inflammatory cells during rejection has not been elucidated, which is a key step for the introduction of novel biomarkers in the clinics. We immunophenotyped glomerulitis during episodes of acute rejection in order to investigate their predictive value for transplant outcomes. To do so, we included 57 transplant biopsies of 57 renal transplant recipients with biopsy-proven acute rejection with a median follow-up of 4.2 years. We determined average glomerular cell counts for T cells, B cells, Tregs, IL-17(+) cells, neutrophils and macrophages. Logistic and Cox regression models were used to investigate the association of glomerular inflammatory cells with response to therapy and graft failure on a population level. We used novel time-dependent ROC curve analyses to investigate the value of glomerular inflammatory cell infiltrates for the prediction of transplant outcomes, applicable to the individual patient. We identified three cell types that were responsible for glomerulitis during rejection: macrophages, T cells and neutrophils. By quantification of glomerular macrophages, an emerging cell type associated with antibody-mediated rejection, we were able to predict the progression towards death-censored graft failure within the first 500 days after the initial episode of rejection. With the use of novel time-dependent ROC analyses, we propose dynamic sensitivities, specificities, and positive and negative predictive values with their corresponding cut-off values for the average amount of glomerular macrophages, depending on what time after rejection death-censored graft failure needs predictio

The impact of the COVID-19 pandemic on Sexually Transmitted Infections surveillance data: incidence drop or artefact?

Background Before the COVID-19 pandemic, Sexually transmitted infections (STIs) were increasing in Europe, and Spain and Catalonia were not an exception. Catalonia has been one of the regions with the highest number of COVID-19 confirmed cases in Spain. The objective of this study was to estimate the magnitude of the decline, due to the COVID-19 pandemic, in the number of STI confirmed cases in Catalonia during the lockdown and de-escalation phases. Methods Interrupted time series analysis was performed to estimate the magnitude of decline in the number of STI reported confirmed cases - chlamydia, gonorrhoea, syphilis, and lymphogranuloma venereum- in Catalonia since lockdown with historical data, from March 13th to August 1st 2020, comparing the observed with the expected values. Results We found that since the start of COVID-19 pandemic the number of STI reported cases was 51% less than expected, reaching an average of 56% during lockdown (50% and 45% during de-escalation and new normality) with a maximum decrease of 72% for chlamydia and minimum of 22% for syphilis. Our results indicate that fewer STIs were reported in females, people living in more deprived areas, people with no previous STI episodes during the last three years, and in the HIV negative. Conclusions The STI notification sharp decline was maintained almost five months after lockdown started, well into the new normality. This fact can hardly be explained without significant underdiagnosis and underreporting. There is an urgent need to strengthen STI/HIV diagnostic programs and services, as well as surveillance, as the pandemic could be concealing the real size of the already described re-emergence of STIs in most of the European countries

Prenatal and postnatal exposure to NO2 and child attentional function at 4-5 years of age

BACKGROUND: Prenatal and postnatal exposure to air pollution has been linked to cognitive impairment in children, but very few studies have assessed its association with attentional function. OBJECTIVES: To evaluate the association between prenatal and postnatal exposure to nitrogen dioxide (NO2) and attentional function in children at 4-5years of age. METHODS: We used data from four regions of the Spanish INMA-Environment and Childhood-Project, a population-based birth cohort. Using land-use regression models (LUR), we estimated prenatal and postnatal NO2 levels in all of these regions at the participants' residential addresses. We assessed attentional function using the Kiddie-Conners Continuous Performance Test (K-CPT). We combined the region-specific adjusted effect estimates using random-effects meta-analysis. RESULTS: We included 1298 children with complete data. Prenatal exposure to NO2 was associated with an impaired standard error of the hit reaction time (HRT(SE)) (increase of 1.12ms [95% CI; 0.22 a 2.02] per 10μg/m3 increase in prenatal NO2) and increased omission errors (6% [95% CI; 1.01 to 1.11] per 10μg/m3 increase in prenatal NO2). Postnatal exposure to NO2 resulted in a similar but borderline significant increase of omission errors (5% [95% CI; =0.99 to 1.11] per 10μg/m3 increase in postnatal NO2). These associations did not vary markedly between regions, and were mainly observed in girls. Commission errors and lower detectability were associated with prenatal and postnatal exposure to NO2 only in some regions. CONCLUSIONS: This study indicates that higher exposure to ambient NO2, mainly during pregnancy and to a lesser extent postnatally, is associated with impaired attentional function in children at 4-5years of age.This study was funded by grants from the Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041 and PI031615; PI041931; PI041112; PI041436; PI041509; PI042018; PI051079; PI051052; PI060867; PI061213; PI070314; CP1100178; PI081151 incl. FEDER funds; PS0900090 incl. FEDER funds; PI0902311 incl. FEDER funds; PI0902647 incl. FEDER funds; PI1102591 incl. FEDER funds; PI1102038 incl. FEDER funds; PI131944 incl. FEDER funds; PI132032 incl. FEDER funds; PI1302429 incl. FEDER funds; PI1302187 incl. FEDER funds; PI140891 incl. FEDER funds; PI141687 incl. FEDER funds and MS13/00054), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), Department of Health of the Basque Government (2005111093, 2009111069 and 2013111089), the Provincial Government of Gipuzkoa (DFG06/002 and DFG08/001), Convenios anuales con los ayuntamientos de la zona del estudio (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain), from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), from the European Research Council under the ERC Grant Agreement number ERC-AdG 2010 GA#268479 – the BREATHE project, from the Conselleria de Sanitat of Generalitat Valenciana (AP212/11, 002/008, 012/009, 013/2009, 014/009, 015/008, 016/009, 021/007, 021/008, 023/008 and 024/007) and from Obra Social Cajastur/Fundación Liberbank and Universidad de Oviedo. ISGlobal is a member of the CERCA Programme, Generalitat de Cataluny